Delivery of diagnostic drugs via nanobubbles has shown to be an emerging field of study. Due to their small size, nanobubbles may more easily travel through constricted blood vessels and precisely target certain bodily parts. Nanobubble is considered the major treatment for cancer treatment and other diseases which are difficult to diagnose. The field of nanobubbles is dynamic and continues to grow as researchers discover new properties and seek practical applications in various fields. The predominant usage of nanobubbles in novel drug delivery is to enhance the bioavailability, and controlled drug release along with imaging properties Nanobubbles are important because they may change interfacial characteristics including surface force, lubrication, and absorption. The quick diffusion of gas into the water was caused by a hypothetical film that was stimulated and punctured by a strong acting force at the gas/water contact of the bubble. In this article, various prominent aspects of nanobubbles have been discussed, along with the long-acting nature, and the theranostical aspect which elucidates the potential marketed drugs along with clinical trial products. The article also covers quality by design aspects, different production techniques that enable method-specific therapeutic applications, increasing the floating time of the bubble, and refining its properties to enhance the prepared nanobubble's quality. Nanobubble containing both analysis and curing properties makes it special from other nano-carriers. This work includes all the possible methods of preparing nanobubble, its application, all marketed drugs, and products in clinical trials.
{"title":"A Systematic Study on Long-acting Nanobubbles: Current Advancement and Prospects on Theranostic Properties","authors":"Gokulnath Jayasankar, Jebastin Koilpillai, Damodharan Narayanasamy","doi":"10.34172/apb.2024.042","DOIUrl":"https://doi.org/10.34172/apb.2024.042","url":null,"abstract":"Delivery of diagnostic drugs via nanobubbles has shown to be an emerging field of study. Due to their small size, nanobubbles may more easily travel through constricted blood vessels and precisely target certain bodily parts. Nanobubble is considered the major treatment for cancer treatment and other diseases which are difficult to diagnose. The field of nanobubbles is dynamic and continues to grow as researchers discover new properties and seek practical applications in various fields. The predominant usage of nanobubbles in novel drug delivery is to enhance the bioavailability, and controlled drug release along with imaging properties Nanobubbles are important because they may change interfacial characteristics including surface force, lubrication, and absorption. The quick diffusion of gas into the water was caused by a hypothetical film that was stimulated and punctured by a strong acting force at the gas/water contact of the bubble. In this article, various prominent aspects of nanobubbles have been discussed, along with the long-acting nature, and the theranostical aspect which elucidates the potential marketed drugs along with clinical trial products. The article also covers quality by design aspects, different production techniques that enable method-specific therapeutic applications, increasing the floating time of the bubble, and refining its properties to enhance the prepared nanobubble's quality. Nanobubble containing both analysis and curing properties makes it special from other nano-carriers. This work includes all the possible methods of preparing nanobubble, its application, all marketed drugs, and products in clinical trials.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140390883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Many people lose their lives to cancer each year. The prevalence of illnesses, metabolic disorders, high-risk infections, and other conditions has been greatly slowed down by expanding scientific research. Chemotherapy and radiation are still the initial lines of treatment for cancer patients, along with surgical removal of tumors. Modifications have been made in chemotherapy since medicines frequently have substantial systemic toxicity and poor pharmacokinetics and still do not reach the tumor site at effective concentrations. Chemotherapy may now be administered more safely and effectively thanks to nanotechnology. Nanotechnology-based graphene quantum dots are very applicable in breast cancer detection, as a drug delivery system, and in the treatment of breast cancer because of their physical and chemical properties, less toxicity, small size, fluorescence, and effective drug delivery. This paper analyzes the graphene quantum dots as cutting-edge platforms for biotechnology and nanomedicine also its application in drug delivery in cancer. It shows that graphene quantum dots can be effectively conjugated with Hyaluronic Acid to achieve efficient and target-specific delivery.
{"title":"Review on Hyaluronic Acid Functionalized Sulfur and Nitrogen Co-Doped Graphene Quantum Dots Nano Conjugates for Targeting of Specific type of Cancer.","authors":"Kedar Bavaskar, Vinit Patil, Dilip Morani, Ashish Jain","doi":"10.34172/apb.2024.043","DOIUrl":"https://doi.org/10.34172/apb.2024.043","url":null,"abstract":"Many people lose their lives to cancer each year. The prevalence of illnesses, metabolic disorders, high-risk infections, and other conditions has been greatly slowed down by expanding scientific research. Chemotherapy and radiation are still the initial lines of treatment for cancer patients, along with surgical removal of tumors. Modifications have been made in chemotherapy since medicines frequently have substantial systemic toxicity and poor pharmacokinetics and still do not reach the tumor site at effective concentrations. Chemotherapy may now be administered more safely and effectively thanks to nanotechnology. Nanotechnology-based graphene quantum dots are very applicable in breast cancer detection, as a drug delivery system, and in the treatment of breast cancer because of their physical and chemical properties, less toxicity, small size, fluorescence, and effective drug delivery. This paper analyzes the graphene quantum dots as cutting-edge platforms for biotechnology and nanomedicine also its application in drug delivery in cancer. It shows that graphene quantum dots can be effectively conjugated with Hyaluronic Acid to achieve efficient and target-specific delivery.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140391005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aysan Eslami Abriz, A. Araghi, Mahdieh Nemati, Maryam Taghavi Narmi, M. Ahmadi, Fatemeh Abedini, R. Keyhanmanesh, Fariba Ghiasi, R. Rahbarghazi
Purpose: Among varied ω-3 polyunsaturated fatty acid types, the therapeutic properties of Docosahexaenoic acid (DHA) have been indicated under diabetic conditions in different cell lineages. Here, we investigated the anti-diabetic properties of DHA in rats with type 2 diabetes mellitus (D2M) focusing on autophagy-controlling factors. Methods: D2M was induced in male Wistar rats using a single dose of Streptozocin (STZ) and a high-fat diet for 8 weeks. On week 2, diabetic rats received DHA 950 mg/kg/day until the end of the study. After that, rats were euthanized, and aortic and cardiac tissue samples were stained with H&E staining for histological assessment. The expression of adhesion molecules, ICAM-1 and VCAM-1, was measured in heart samples using real-time PCR analysis. Using western blotting, protein levels of BCLN1, LC3, and P62 were measured in D2M rats pre- and post-DHA treatment. Results: Data showed intracellular lipid vacuoles inside the vascular cells, and cardiomyocytes, after induction of D2M and DHA reduced intracellular lipid droplets and in situ inflammatory response. DHA can diminish increased levels of ICAM-1 in diabetic conditions (pControl VS. D2M rats = 0.005) and reach near-to-control values (pControl VS. D2M rats = 0.28; pD2M rats VS. D2M rats + DHA =0.033). Based on western blotting, D2M slightly increased the BCLN1 and LC3-II/I ratio without affecting P62. DHA promoted the LC3II/I ratio (p = 0.303) and reduced P62 (pControl VS. D2M rats + DHA =0.0433; pD2M VS. D2M rats + DHA =0.096), leading to the completion of autophagy flux under diabetic conditions. Conclusion: DHA can reduce lipotoxicity of cardiovascular cells possibly via the activation of adaptive autophagy response in D2D rats.
目的：在各种ω-3 多不饱和脂肪酸中，二十二碳六烯酸（DHA）的治疗特性已在不同细胞系的糖尿病条件下得到证实。在此，我们研究了 DHA 在 2 型糖尿病（D2M）大鼠体内的抗糖尿病特性，重点是自噬控制因子。研究方法使用单剂量链脲佐菌素（STZ）和高脂饮食诱导雄性 Wistar 大鼠患 2 型糖尿病（D2M）8 周。第 2 周，糖尿病大鼠接受 DHA 950 毫克/千克/天，直至研究结束。之后，大鼠被安乐死，主动脉和心脏组织样本经 H&E 染色后进行组织学评估。使用实时 PCR 分析测定心脏样本中粘附分子 ICAM-1 和 VCAM-1 的表达。使用 Western 印迹法测定了 D2M 大鼠在接受 DHA 治疗前后 BCLN1、LC3 和 P62 的蛋白水平。结果显示数据显示，诱导 D2M 后，血管细胞和心肌细胞内的细胞内脂质空泡和 DHA 减少了细胞内脂滴和原位炎症反应。DHA 能降低糖尿病条件下 ICAM-1 水平的升高（pControl VS. D2M rats = 0.005），并达到接近控制值（pControl VS. D2M rats = 0.28; pD2M rats VS. D2M rats + DHA =0.033）。根据西方印迹法，D2M 会轻微增加 BCLN1 和 LC3-II/I 比率，但不会影响 P62。DHA促进了LC3II/I比率（p = 0.303），降低了P62（pControl VS. D2M rats + DHA =0.0433; pD2M VS. D2M rats + DHA =0.096），导致糖尿病条件下自噬通量的完成。结论DHA 可降低心血管细胞的脂肪毒性，这可能是通过激活 D2D 大鼠的适应性自噬反应实现的。
{"title":"Docosahexaenoic acid reduced vascular endothelial cell injury in diabetic rats via the modulation of autophagy","authors":"Aysan Eslami Abriz, A. Araghi, Mahdieh Nemati, Maryam Taghavi Narmi, M. Ahmadi, Fatemeh Abedini, R. Keyhanmanesh, Fariba Ghiasi, R. Rahbarghazi","doi":"10.34172/apb.2024.039","DOIUrl":"https://doi.org/10.34172/apb.2024.039","url":null,"abstract":"Purpose: Among varied ω-3 polyunsaturated fatty acid types, the therapeutic properties of Docosahexaenoic acid (DHA) have been indicated under diabetic conditions in different cell lineages. Here, we investigated the anti-diabetic properties of DHA in rats with type 2 diabetes mellitus (D2M) focusing on autophagy-controlling factors. Methods: D2M was induced in male Wistar rats using a single dose of Streptozocin (STZ) and a high-fat diet for 8 weeks. On week 2, diabetic rats received DHA 950 mg/kg/day until the end of the study. After that, rats were euthanized, and aortic and cardiac tissue samples were stained with H&E staining for histological assessment. The expression of adhesion molecules, ICAM-1 and VCAM-1, was measured in heart samples using real-time PCR analysis. Using western blotting, protein levels of BCLN1, LC3, and P62 were measured in D2M rats pre- and post-DHA treatment. Results: Data showed intracellular lipid vacuoles inside the vascular cells, and cardiomyocytes, after induction of D2M and DHA reduced intracellular lipid droplets and in situ inflammatory response. DHA can diminish increased levels of ICAM-1 in diabetic conditions (pControl VS. D2M rats = 0.005) and reach near-to-control values (pControl VS. D2M rats = 0.28; pD2M rats VS. D2M rats + DHA =0.033). Based on western blotting, D2M slightly increased the BCLN1 and LC3-II/I ratio without affecting P62. DHA promoted the LC3II/I ratio (p = 0.303) and reduced P62 (pControl VS. D2M rats + DHA =0.0433; pD2M VS. D2M rats + DHA =0.096), leading to the completion of autophagy flux under diabetic conditions. Conclusion: DHA can reduce lipotoxicity of cardiovascular cells possibly via the activation of adaptive autophagy response in D2D rats.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140390824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abolfazl Soulat, Taghi mohsenpour, Leila Roshangar, H. Naghshara
The study examines the induction of apoptosis in colon cancer stem cells (CCSCs) within a 3D culture setting, employing an innovative cold atmospheric plasma (CAP) transmission method known as TS-TCAP. TS-TCAP is a partially or fully ionized non-thermal gaseous mixture that comprises photons, charged and neutral particles, and free radicals, which has gained traction in biomedical applications such as cancer therapy. TS-TCAP impacts CCSCs via a continuous, two-step transport process, facilitating the efficient delivery of reactive oxygen and nitrogen species (RONS). The key cellular factors of CCSCs impacted by TS-TCAP treatment, encompassing the secretion and expression levels of IL-6 and IL-8, apoptotic cell count, and expression of BAX, BCL-2, and KI-67 proteins, were evaluated using qrt-ELISA, Annexin V, and qrt-PCR procedures, respectively. The outcomes of CCSCs treatment with TS-TCAP reveal a notable rise in the number of apoptotic cells (p value <0.0001), diminished secretion, and gene expression of IL-6 and IL-8 (p-value < 0.0001), accompanied by favorable alterations in BCL-2 and BAX gene expression (p value <0.0001). Additionally, a notable decrease in KI-67 expression was observed, correlating with a reduction in CCSCs proliferation (p value <0.0001). As well, this study underscores the anti-cancer potential of TS-TCAP, showcasing its efficacy in reducing CCSCs survival rates. However, further pre-clinical and clinical trials are necessary to evaluate CAP's efficacy, safety, and potential synergistic effects with other therapies thoroughly. Overall, TS-TCAP presents a promising alternative for CCSCs treatment, pending further investigation and refinement.
{"title":"A Two-Stage Transferred Cold Atmospheric Plasma as a Unique Therapeutic Strategy for Targeting Colon Cancer Stem Cells","authors":"Abolfazl Soulat, Taghi mohsenpour, Leila Roshangar, H. Naghshara","doi":"10.34172/apb.2024.041","DOIUrl":"https://doi.org/10.34172/apb.2024.041","url":null,"abstract":"The study examines the induction of apoptosis in colon cancer stem cells (CCSCs) within a 3D culture setting, employing an innovative cold atmospheric plasma (CAP) transmission method known as TS-TCAP. TS-TCAP is a partially or fully ionized non-thermal gaseous mixture that comprises photons, charged and neutral particles, and free radicals, which has gained traction in biomedical applications such as cancer therapy. TS-TCAP impacts CCSCs via a continuous, two-step transport process, facilitating the efficient delivery of reactive oxygen and nitrogen species (RONS). The key cellular factors of CCSCs impacted by TS-TCAP treatment, encompassing the secretion and expression levels of IL-6 and IL-8, apoptotic cell count, and expression of BAX, BCL-2, and KI-67 proteins, were evaluated using qrt-ELISA, Annexin V, and qrt-PCR procedures, respectively. The outcomes of CCSCs treatment with TS-TCAP reveal a notable rise in the number of apoptotic cells (p value <0.0001), diminished secretion, and gene expression of IL-6 and IL-8 (p-value < 0.0001), accompanied by favorable alterations in BCL-2 and BAX gene expression (p value <0.0001). Additionally, a notable decrease in KI-67 expression was observed, correlating with a reduction in CCSCs proliferation (p value <0.0001). As well, this study underscores the anti-cancer potential of TS-TCAP, showcasing its efficacy in reducing CCSCs survival rates. However, further pre-clinical and clinical trials are necessary to evaluate CAP's efficacy, safety, and potential synergistic effects with other therapies thoroughly. Overall, TS-TCAP presents a promising alternative for CCSCs treatment, pending further investigation and refinement.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140391036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fahime Nasr Esfahani, Sahand Karimi, Zahra Jalilian, Mehran Alavi, Bushra Aziz, Enam Alhagh Charkhat Gorgich, M. R. Mozafari, Elham Taghavi, sargol aminnezhad, Sara Ataei
Photodynamic therapy (PDT) is a multidisciplinary area, which involves photophysics and photochemical sciences and plays an important role in cancer diagnosis and treatment. PDT involves a photo-activable drug called photosensitizer (PS), a specific wavelength of light and cellular compounds to produce toxic oxygen species in a much-localized way to destroy malignant tumors. Despite the various benefits of PDT, some PS-related limitations hinder its use as an ideal treatment option for cancer. To address these limitations (e.g., poor bioavailability, weak permeability, hydrophobicity, and aggregation), lipid-based and vesicular drug delivery systems have been employed. These carrier systems possess the ability to enhance the bioavailability, permeability, and solubility of the drug. Furthermore, they tend to load hydrophobic and lipophilic compounds and can be employed for an efficient and targeted drug delivery. The purpose of this review is to highlight the precise idea of PDT, the limitations of PDT related to PS, and the application of lipidic and tocosomal carriers in PDT for the treatment of various types of cancers. Liposomes, nanoliposomes, solid lipid nanoparticles, vesicular phospholipid gels, exosomes, transferosomes, and tocosomes are presented as commonly–employed vesicular drug carriers. Moreover, the amalgamation of cell-based drug delivery systems (CBDDS) with PDT holds considerable potential as an encouraging avenue in cancer treatment, especially in the context of immunotherapy.
{"title":"Functionalized and theranostic lipidic and tocosomal drug delivery systems: potentials and limitations in cancer photodynamic therapy","authors":"Fahime Nasr Esfahani, Sahand Karimi, Zahra Jalilian, Mehran Alavi, Bushra Aziz, Enam Alhagh Charkhat Gorgich, M. R. Mozafari, Elham Taghavi, sargol aminnezhad, Sara Ataei","doi":"10.34172/apb.2024.038","DOIUrl":"https://doi.org/10.34172/apb.2024.038","url":null,"abstract":"Photodynamic therapy (PDT) is a multidisciplinary area, which involves photophysics and photochemical sciences and plays an important role in cancer diagnosis and treatment. PDT involves a photo-activable drug called photosensitizer (PS), a specific wavelength of light and cellular compounds to produce toxic oxygen species in a much-localized way to destroy malignant tumors. Despite the various benefits of PDT, some PS-related limitations hinder its use as an ideal treatment option for cancer. To address these limitations (e.g., poor bioavailability, weak permeability, hydrophobicity, and aggregation), lipid-based and vesicular drug delivery systems have been employed. These carrier systems possess the ability to enhance the bioavailability, permeability, and solubility of the drug. Furthermore, they tend to load hydrophobic and lipophilic compounds and can be employed for an efficient and targeted drug delivery. The purpose of this review is to highlight the precise idea of PDT, the limitations of PDT related to PS, and the application of lipidic and tocosomal carriers in PDT for the treatment of various types of cancers. Liposomes, nanoliposomes, solid lipid nanoparticles, vesicular phospholipid gels, exosomes, transferosomes, and tocosomes are presented as commonly–employed vesicular drug carriers. Moreover, the amalgamation of cell-based drug delivery systems (CBDDS) with PDT holds considerable potential as an encouraging avenue in cancer treatment, especially in the context of immunotherapy.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140253763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Chen, Xun Qin, Wen Bai, Jun-Song Ren, Yang Yu, Huiling Nie, Xiumiao Li, Zhangyu Liu, Jiayu Huang, Juxue Li, Jin Yao, Qin Jiang
Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (VEGF) drugs, including Bevacizumab, Ranibizumab, and Aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. Recently, inflammation has been identified as one of the main risk factors in the progression of AMD. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Materials and methods: Various experiments were conducted to assess the Kavain’s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-Ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a Laser-induced CNV mice model. Laser burns, approximately two papillary diameters away from the mouse optic nerve, were uniformly induced (532 nm wavelength, 0.1 s duration, 120 mW power, and 50 µm spot size). To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus Aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE) /choroid complexes (P<0.05). Mechanistically, we proved that Kavain decreased the activity of the hypoxia-inducible factor 1 α (HIF-1 α)/VEGF-A/VEGF receptor 2 (VEGFR2) signaling pathway. Conclusions: Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.
{"title":"Kavain alleviates choroidal neovascularization via decreasing the activity of the HIF-1α/VEGF-A/VEGFR2 signaling pathway and inhibiting inflammation","authors":"Xi Chen, Xun Qin, Wen Bai, Jun-Song Ren, Yang Yu, Huiling Nie, Xiumiao Li, Zhangyu Liu, Jiayu Huang, Juxue Li, Jin Yao, Qin Jiang","doi":"10.34172/apb.2024.036","DOIUrl":"https://doi.org/10.34172/apb.2024.036","url":null,"abstract":"Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (VEGF) drugs, including Bevacizumab, Ranibizumab, and Aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. Recently, inflammation has been identified as one of the main risk factors in the progression of AMD. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Materials and methods: Various experiments were conducted to assess the Kavain’s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-Ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a Laser-induced CNV mice model. Laser burns, approximately two papillary diameters away from the mouse optic nerve, were uniformly induced (532 nm wavelength, 0.1 s duration, 120 mW power, and 50 µm spot size). To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus Aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE) /choroid complexes (P<0.05). Mechanistically, we proved that Kavain decreased the activity of the hypoxia-inducible factor 1 α (HIF-1 α)/VEGF-A/VEGF receptor 2 (VEGFR2) signaling pathway. Conclusions: Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140252626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
mohammad sadegh hashemzadeh, Hadi Esmaeili Gouvarchin Ghaleh, Mozafar Mohammadi, Yaser Yousefpoor, Ehsan Rezaei, Gholamhossein Alishiri
Purpose: Rheumatoid arthritis (RA) is a type of autoimmune disease that results in chronic inflammation of the joint synovial tissue, leading to joint damage and significant disability. Despite ongoing research, the exact cause of RA remains unclear, and current treatments have limitations. This study explores the potential of utilizing interleukin-1 receptor antagonist (IL-1RA) and anti-inflammatory macrophages polarized in the vicinity of the supernatant from allogeneic mesenchymal stem cells (MSCs) as a novel therapeutic approach for RA. Methods: An expression cassette containing the IL-1RA gene was constructed and expressed in E. coli BL21. The resulting protein was purified and stabilized for use in in vivo experiments. Bone marrow MSCs were isolated and used to produce anti-inflammatory M2 macrophages from the isolated peripheral blood monocytes. The macrophages were then used to treat mice with RA induced by collagen type II. Results: The combination of IL-1RA and M2 macrophages improved clinical and histopathological symptoms of the disease, reduced levels of inflammatory factors, and modulated the immune system in the treated mouse groups. The results showed that this combinatory therapy had a synergistic effect for RA treatment. Conclusion: The simultaneous use of IL-1RA and M2 cells could be a promising approach for the treatment of RA. This combinatory therapy has the potential to improve the disease and decrease the severity of inflammation in patients with RA. Keywords: Rheumatoid arthritis, IL-1RA, Anti-inflammatory macrophages, Synergistic effect, Novel therapeutic approach and Combinatory therapy
目的：类风湿性关节炎（RA）是一种自身免疫性疾病：类风湿性关节炎（RA）是一种自身免疫性疾病，会导致关节滑膜组织慢性炎症，造成关节损伤和严重残疾。尽管研究仍在进行，但 RA 的确切病因仍不清楚，目前的治疗方法也有局限性。本研究探讨了利用白细胞介素-1受体拮抗剂（IL-1RA）和在异体间充质干细胞（MSCs）上清液附近极化的抗炎巨噬细胞治疗RA的可能性。方法：构建含有IL-1RA基因的表达盒，并在大肠杆菌BL21中表达。纯化并稳定所得到的蛋白，用于体内实验。分离骨髓间充质干细胞，并用其从分离的外周血单核细胞中产生抗炎的 M2 巨噬细胞。然后用巨噬细胞治疗由 II 型胶原诱导的 RA 小鼠。研究结果IL-1RA和M2巨噬细胞的联合治疗改善了小鼠的临床和组织病理学症状，降低了炎症因子的水平，并调节了治疗组小鼠的免疫系统。结果表明，这种联合疗法对治疗 RA 有协同作用。结论同时使用IL-1RA和M2细胞可能是治疗RA的一种很有前景的方法。这种联合疗法有可能改善 RA 患者的病情并减轻炎症的严重程度。关键词类风湿性关节炎 IL-1RA 抗炎巨噬细胞 协同效应 新型治疗方法 联合疗法
{"title":"Therapeutic Effects of IL-1RA, M2 Cells, and their Synergistic Impact on a Mouse Model of Rheumatoid Arthritis","authors":"mohammad sadegh hashemzadeh, Hadi Esmaeili Gouvarchin Ghaleh, Mozafar Mohammadi, Yaser Yousefpoor, Ehsan Rezaei, Gholamhossein Alishiri","doi":"10.34172/apb.2024.037","DOIUrl":"https://doi.org/10.34172/apb.2024.037","url":null,"abstract":"Purpose: Rheumatoid arthritis (RA) is a type of autoimmune disease that results in chronic inflammation of the joint synovial tissue, leading to joint damage and significant disability. Despite ongoing research, the exact cause of RA remains unclear, and current treatments have limitations. This study explores the potential of utilizing interleukin-1 receptor antagonist (IL-1RA) and anti-inflammatory macrophages polarized in the vicinity of the supernatant from allogeneic mesenchymal stem cells (MSCs) as a novel therapeutic approach for RA. Methods: An expression cassette containing the IL-1RA gene was constructed and expressed in E. coli BL21. The resulting protein was purified and stabilized for use in in vivo experiments. Bone marrow MSCs were isolated and used to produce anti-inflammatory M2 macrophages from the isolated peripheral blood monocytes. The macrophages were then used to treat mice with RA induced by collagen type II. Results: The combination of IL-1RA and M2 macrophages improved clinical and histopathological symptoms of the disease, reduced levels of inflammatory factors, and modulated the immune system in the treated mouse groups. The results showed that this combinatory therapy had a synergistic effect for RA treatment. Conclusion: The simultaneous use of IL-1RA and M2 cells could be a promising approach for the treatment of RA. This combinatory therapy has the potential to improve the disease and decrease the severity of inflammation in patients with RA. Keywords: Rheumatoid arthritis, IL-1RA, Anti-inflammatory macrophages, Synergistic effect, Novel therapeutic approach and Combinatory therapy","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140251567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Negar Sedghi Aminabad, Yousef Saeedi, Jamal Adiban, Mahdieh Nemati, Donya Shaterabadi, Farhood Najafi, Reza Rahbarghazi, Mehdi Talebi, A. Zarebkohan
Receptor-mediated transcytosis (RMT) is a more specific, highly efficient, and reliable approach to crossing the blood-brain-barrier (BBB) for the entry of therapeutic cargos into the brain parenchyma. Here, we introduced and characterized a human-specific novel leptin-derived peptide, using in silico and in vitro experiments. Using bioinformatic analysis and molecular dynamics (MD) simulation, a 14 amino acid peptide sequence (LDP14) was isolated and its interaction with leptin-receptor (ObR) was analyzed compared to Lep30 (as the most efficient leptin-derived peptide in targeting the brain). MD simulation data revealed a significant stable interaction between ligand binding domains (LBD) of ObR with LDP14 more than that of Lep30. Analyses demonstrated suitable cellular uptake of LDP14 and selectively targeting ability for human capillary endothelial cells (hBCEC-D3) and human U87 glioma cell lines compared to Lep30, in RMT, and energy-dependent manner. Data exhibited that LDP14 was unable to enter the rat C6 glioma cells, indicating the species specificity of this peptide. Likewise, data confirmed that the internalization of LDP14-modified G4 PAMAM dendrimers and their polyplex derivative with pEGFP-N1 plasmid occurs in ObR and species-dependent manner. Finally, our findings illustrated that the entry of LDP14-modified dendrimers in hBCEC-D3 cells not only was not affected by protein corona (PC) formation but also PC per se can enhance uptake rate. Commensurate with these descriptions, LDP14 can be used in the delivery of drugs/genes to the brain tissue with great potential application. Besides, there is no need for manipulations for overcoming the undesirable effects of blood proteins on the fate of therapeutic cargo targeting.
{"title":"Discovery of a novel dual targeting peptide for human glioma: from in-silico simulation to acting as targeting ligand","authors":"Negar Sedghi Aminabad, Yousef Saeedi, Jamal Adiban, Mahdieh Nemati, Donya Shaterabadi, Farhood Najafi, Reza Rahbarghazi, Mehdi Talebi, A. Zarebkohan","doi":"10.34172/apb.2024.033","DOIUrl":"https://doi.org/10.34172/apb.2024.033","url":null,"abstract":"Receptor-mediated transcytosis (RMT) is a more specific, highly efficient, and reliable approach to crossing the blood-brain-barrier (BBB) for the entry of therapeutic cargos into the brain parenchyma. Here, we introduced and characterized a human-specific novel leptin-derived peptide, using in silico and in vitro experiments. Using bioinformatic analysis and molecular dynamics (MD) simulation, a 14 amino acid peptide sequence (LDP14) was isolated and its interaction with leptin-receptor (ObR) was analyzed compared to Lep30 (as the most efficient leptin-derived peptide in targeting the brain). MD simulation data revealed a significant stable interaction between ligand binding domains (LBD) of ObR with LDP14 more than that of Lep30. Analyses demonstrated suitable cellular uptake of LDP14 and selectively targeting ability for human capillary endothelial cells (hBCEC-D3) and human U87 glioma cell lines compared to Lep30, in RMT, and energy-dependent manner. Data exhibited that LDP14 was unable to enter the rat C6 glioma cells, indicating the species specificity of this peptide. Likewise, data confirmed that the internalization of LDP14-modified G4 PAMAM dendrimers and their polyplex derivative with pEGFP-N1 plasmid occurs in ObR and species-dependent manner. Finally, our findings illustrated that the entry of LDP14-modified dendrimers in hBCEC-D3 cells not only was not affected by protein corona (PC) formation but also PC per se can enhance uptake rate. Commensurate with these descriptions, LDP14 can be used in the delivery of drugs/genes to the brain tissue with great potential application. Besides, there is no need for manipulations for overcoming the undesirable effects of blood proteins on the fate of therapeutic cargo targeting.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140255759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer is one of the main causes of mortality worldwide. Cancer cells are characterized by unregulated cellular processes, including proliferation, progression, and angiogenesis. The occurrence of these processes is due to the dysregulation of various signaling pathways such as NF-κB (nuclear factor-κB), Wnt/beta-catenin, Notch signaling and MAPK (mitogen-activated protein kinases). Notch signaling pathways cause the progression of various types of malignant tumors. Among the phytochemicals for cancer therapy, several have attracted great interest, including curcumin, genistein, quercetin, silibinin, resveratrol, cucurbitacin and glycyrrhizin. Given the great cellular and molecular heterogeneity within tumors and the high toxicity and side effects of synthetic chemotherapeutics, natural products with pleiotropic effects that simultaneously target numerous signaling pathways appear to be ideal substitutes for cancer therapy. With this in mind, we take a look at the current status, impact and potential of known compounds as golden phytochemicals on key signaling pathways in tumors, focusing on the Notch pathway. This review may be useful for discovering new molecular targets for safe and efficient cancer therapy with natural chemotherapeutics.
{"title":"Notch Signaling Suppression by Golden Phytochemicals: Potential for Cancer Therapy","authors":"Masoumeh Kaveh Zenjanab, Nastaran Hashemzadeh, sajjad mohamadvand, Masoumeh Sharifi-Azad, Elaheh Dalir Abdolahinia, rana jahanban-esfahlan","doi":"10.34172/apb.2024.035","DOIUrl":"https://doi.org/10.34172/apb.2024.035","url":null,"abstract":"Cancer is one of the main causes of mortality worldwide. Cancer cells are characterized by unregulated cellular processes, including proliferation, progression, and angiogenesis. The occurrence of these processes is due to the dysregulation of various signaling pathways such as NF-κB (nuclear factor-κB), Wnt/beta-catenin, Notch signaling and MAPK (mitogen-activated protein kinases). Notch signaling pathways cause the progression of various types of malignant tumors. Among the phytochemicals for cancer therapy, several have attracted great interest, including curcumin, genistein, quercetin, silibinin, resveratrol, cucurbitacin and glycyrrhizin. Given the great cellular and molecular heterogeneity within tumors and the high toxicity and side effects of synthetic chemotherapeutics, natural products with pleiotropic effects that simultaneously target numerous signaling pathways appear to be ideal substitutes for cancer therapy. With this in mind, we take a look at the current status, impact and potential of known compounds as golden phytochemicals on key signaling pathways in tumors, focusing on the Notch pathway. This review may be useful for discovering new molecular targets for safe and efficient cancer therapy with natural chemotherapeutics.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140254711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Khaledian, Ghobad Mohammadi, M. Abdoli, Arad Fatahian, Arya Fatahian, Reza Fatahian
Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.
{"title":"Recent advances in implantable 3D-printed scaffolds for repair of spinal cord injury","authors":"S. Khaledian, Ghobad Mohammadi, M. Abdoli, Arad Fatahian, Arya Fatahian, Reza Fatahian","doi":"10.34172/apb.2024.032","DOIUrl":"https://doi.org/10.34172/apb.2024.032","url":null,"abstract":"Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140254857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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